The human brain differs greatly from those of other species in the development of a strikingly expanded and extensively folded cerebral neocortex. This feature is considered to underpin humans' augmented intellectual capacity. Human ventricular and subventricular zones also contain more radial glial cells and intermediate progenitors than those of other mammals. To investigate the development of cortical folding, Yu et al. used a three-dimensional culture system to generate cerebral organoids from pluripotent human stem cells. They found that mutations in growth factor signaling—specifically, deletion of PTEN activation of the PI3K-AKT pathway—increased cell-cycle reentry and expanded radial glia and intermediate progenitor populations. The resulting neural progenitor proliferation led to expanded and folded cerebral organoids. Inoculation of the organoids with Zika virus impaired cortical growth and folding.